Exploration on the mechanism of Radix Astragali-Caulis Spatholobi by Qi-invigorating and blood-activating combination for the treatment of atherosclerosis based on network pharmacology

The objective of this study was to investigate the main active ingredients,potential targets,and possible mechanisms of action of the combination of Radix Astragali and Caulis Spatholobi for the treatment of atherosclerosis using network pharmacology.The study aimed to provide a reference basis for the development of new formulations and clinical use of Chinese medicine.The main components of Radix Astragali and Caulis Spatholobi were obtained from the TCMSP,BATMAN-TCM database,and literature reports.The targets corresponding to the main components were imported into the Uniprot database to standardize the names,and target information was supplemented with the Swiss Target Prediction database.Disease-related targets were obtained from DrugBank,OMIM,CTD,GeneCards,and DisGeNET online databases.Venn tools were used to obtain the potential targets of Radix Astragali and Caulis Spatholobi for the treatment of AS.The intersecting genes were imported into the STRING 11.5 database to construct protein-protein interaction network maps and analyze their interactions.Cytoscape 3.7.1 software was used to mine their core targets.GO function and KEGG signaling pathway enrichment analysis were performed using the DAVID v2023q1 database.The results were imported into the“Bioinformatics Cloud Platform”to generate enrichment bubble maps.Finally,the“component-target-pathway”diagram was constructed using Cytoscape 3.7.1 software.The study found that 78 major active ingredients and 527 potential targets were obtained from Radix Astragali and Caulis Spatholobi.The main active components of the two in combination for the treatment of AS are quercetin,stigmasterol,kaempferol,luteolin,formononetin,etc.The key targets involve CDKN1A,E2F1,CDK4,CDK2,CDK1,RB1,TP53,CDKN1B,IL6,JUN,etc.The main pathways involved the AGE-RAGE signaling pathway in diabetic complications,cancer pathway,etc.The biological processes involved include positive regulation of gene expression,negative regulation of apoptotic process,etc.The study initially verified the feasibility of the combination of Radix Astragali-Caulis Spatholobi by Qi-invigorating(promoting human metabolic activity)and blood-activating for the treatment of AS.It demonstrated that the combination of Chinese medicine has multi-level,multi-target,and multi-pathway mechanisms of action to treat the disease,providing a reference basis for the development and utilization of new drugs.

Therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer

Objective:To explore the therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer.Methods:A total of 138 SD rats were selected to make rat models with gastric ulcer induced by acetic acid(24 rats with sham operation served as sham operation group),and were randomly divided into model group(n=30),western medicine group(n=30),traditional Chinese medicine(TCM) group(n=24) and combination group(combined western medicine and TCM group,n=30).Western medicine group was gavaged with omeprazole in the morning and with iso-volumetric distilled water in the afternoon;TCM group and TCM sham operation group were gavaged with iso-volumetric distilled water in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon;combination group was gavaged with omeprazole in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon;sham operation group and model group were gavaged with iso-volumetric distilled water both in the morning and afternoon.Ulcer indexes and degree of mucosal degree in rats at different time points after gavage were observed.Twentyeight days after gavage,interleukin(IL)-1β was given to induce ulcer recurrence so as to observe the recurrent severity and rate of ulcer in each group.Results:Compared with model group and western medicine group,treatment in combination group could prominently reduce the ulcer index of rats with peptic ulcer,and increase the healing rate and inhibition rate of peptic ulcer.After IL-1β-induced ulcer recurrence,combination group was significantly superior to model group and western medicine group in ulcer recurrent rate[50%(3/6) vs.100%(6/6)]and severity.Conclusions:Basic acid-suppression therapy combined with Qi-Replenishing and BloodActivating Formula can effectually improve the ulcer healing quality and reduce ulcer recurrence.

Meta analysis of infertility due to polycystic ovarian syndrome treated by kidney-tonifying and blood-activating therapy

Objective:To explore the Meta-analysis of polycystic ovary syndrome-induced infertility by tonifying kidney and activating blood circulation.Methods:Chinese keywords or subject words such as"kidney-tonifying and Blood-Activating Therapy","polycystic ovary syndrome","infertility"were searched in CNKI,Wanfang and Weipu databases,and English keywords such as"Kidney-tonifying and Blood-Activating Therapy","Stein-Leventhal syndrome","Infertility"were searched in Pubmed database for a period of 2.From 2000 to 2019,Meta-analysis was carried out with Review Manager 5.0.Results:Thirteen randomized controlled literatures were screened out,and the control group was treated with routine western medicine and the treatment group was treated with Kidney-tonifying and Blood-activating therapy.All of them included literatures mentioned grouping method,but no blind method was mentioned,and the literature quality was generally low.Meta-analysis of the effective rate showed that Z=3.69(P=0.0002<0.001),95%CI(1.77,6.42),indicating that the effective rate in the treatment group was higher than that in the control group.Meta-analysis of the cycle ovulation rate showed that Z=2.19(P=0.03<0.05),95%CI(1.08,4.35),indicating that the cycle ovulation rate in the treatment group was higher than that in the control group.Meta-analysis of pregnancy rate showed that:Z=7.07(P<0.00001),95%CI(2.27,4.24),indicating that the pregnancy rate in the treatment group was higher than that in the control group;bias analysis found that the literature was distributed on both sides of the dotted line,most of which were biased.Meta-analysis of the incidence of LUFS showed that Z=3.25(P=0.001<0.05),95%CI(0.02,0.38),indicating that the incidence of LUFS in the treatment group was lower than that in the control group.Meta-analysis of serum E2 level after treatment showed that Z=4.41(P<0.0001),95%CI(11.01,28.64),indicating that the serum E2 level in treatment group was higher than that in control group after treatment.Conclusion:Meta-analysis shows that the method of tonifying kidney and activating blood circulation has a significant effect on infertility caused by polycystic ovary syndrome.It can improve the level of sex hormones,improve the efficiency,cycle ovulation rate and pregnancy rate,and reduce the incidence of LUFS.However,the quality of the included literature is not high,which needs to be further included in high-quality literature to confirm.

Study on the Protective Effects of Compound Blood-activating Soup on Bone Marrow Hematopoietic Cells in Acute Radiation Injured Mice

After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P＜0. 01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen .the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.

Efficacy evaluation of Shenlan oral liquid in the treatment of experimental thrombosis and hyperlipidemia

Objective:To explore the therapeutic effect of Shenlan oral liquid on thrombosis rats and hyperlipidemia mice.Methods:Male Wistar rats were divided into four groups randomly:the control group,the Shenlan oral liquid groups(high dosage and low dosage),and the positive control group.Rats in the control group were treated with dd water intragastriclly;in the positive control group,rats were treated intragastric with aspirin.Rats were treated with different drugs intragastric for continuous 22 d.In the hyperlipidemia experiment,mice were fed with high-fat diet to induce hyperlipidemia model mice,then randomly divided into five groups;the control group,the model group,the atorvastatin calcium positive control group,and the Shenlan oral liquid groups(high dosage and low dosage).The serum lipid and body weight changes of mice were observed after 6 weeks.Animals in Shenlan oral liquid high and low dosage were treated intragastric with six times and double the clinical dose.Results:After treatment,the mix blocking rate and average blocking rate of the vascular after electrical stimulation were obviously reduced in aspirin group,and Shenlan oral liquid high and low dose groups(P<0.05 or P<0.01).The maximum aggregation rate was significantly lower than that of control group(P<0.05 or P<0.01),and the normal coagulation function was not affected.In the treatment of hyperlipidemia,the effects of Shenlan oral liquid were measured on the total cholesterol(TC),triacylglycerol(total triglyceride,TG),low density lipoprotein(LDL-C)and high-density lipoprotein(HDL-C)with the hyperlipidemia mice.After 2 weeks administration,the serum TG level of Shenlan oral liquid high-dose group decreased compared with the model group.The TG level of serum in Shenlan oral liquid high-dose group significantly decreased compared with the model group from the fourth week(P<0.05).After 6 weeks administration,Shenlan oral liquid high-dose and low-dose group and positive drugs reached to the same therapeutic effect.Compared with model group,serum TG level was significantly decreased(P<0.05 or P<0.01).Conclusion:Shenlan oral liquid can decrease the thrombosis formation in rats and inhibit the lipid level in blood in hyperlipidemia mice.

Effect of kidney-reinforcing,blood-activating and stasis-removing recipes on adhesion molecule expression of bone marrow mesenchymal stem cells from chronic aplastic anemia patients

OBJECTIVE： To explore the effect of kidney-rein- forcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone mar- row mesenchymal stem cells （MSCs） from patients with chronic aplastic anemia （CAA）. METHODS： We used three Traditional Chinese Medicine recipes, namely a kidney-reinforcing recipe （KRR）, blood-activating and stasis-removing recipe （BASRR）, and kidney-reinforcing, blood-activating and stasis-removing recipe （KRBASFIR）, and a nor- mal saline control to prepare herbal medicine se- rum in Sprague Dawley rats. Thirty CAA patients were enrolled in the experimental group, including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients. Ten healthy individuals were included in the control group. MSCs were isolated from bone marrow samples, and the cell density was observed to measure their proliferation ability by microscopy on days 2, 7, and 14 after isolation. In addition, the expression of adhesion molecules of bone marrow MSCs （CD106, CD49d, CD31 and CD44） were detected by flow cytometry after 48 h of treatment with the four different herbal medi- cine serums. RESULTS： The proliferation of MSCs from kid- ney-Yang deficient and kidney-Yin deficient pa- tients was weaker than that of MSCs from the con- trol group. The expression of all adhesion mole- cules of bone marrow MSCs from CAA patients was obviously lower than that in the control group （P〈 0.01）. The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was low- er than in those with a kidney-yang deficiency （P〈 0.05 and P〈O.01, respectively）. For kidney-Yang defi- cient patients, CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group （P〈O.01）, while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups （P〈O.01）. For kidney-Yin defi- cient patients, CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group （P〈0.05）, while CD31 and CD44 ex- pression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups （P〈 0.05 and P〈0.01, respectively）. CONCLUSION： The bone marrow microenviron- ment in CAA patients is abnormal. The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin de- ficient patients by improving the expression levels of MSC adhesion molecules.

Blood-activating and Orifice-opening Method with Acupuncture and Moxibustion in Treating Vertebroarterial Cervical Spondylopathy

Objective： It is to investigate the efficacy of the blood-activating and orifice-opening method with acupuncture and moxibusion for treatment of vertebroarterial cervical spondylopathy. Methods： 176 cases were divided into the treatment group （89 cases） and control group （87 cases） randomly.Acupuncture on points Geshu （BL 17）, Fengchi （GB 20） and Bailao （Ex-HN） was applied, and meanwhile moxibustion on points Baihui （GV 20） and Shangxing （GV 23） was applied in the treatment group, while Flunarizine was orally taken in the control group. Results： The bloodactivating and orifice-opening method with acupuncture and moxibustion could significantly improve the comprehensive curative effect clinically, increase the subjective index score and the sign score significantly, and change hemodynamics obviously. Its effect was better than that of the control group. It was also found that its follow-up effect was significantly better that of the control group. Conclusion. The blood-activating and orifice-opening method with acupuncture and moxibustion has a definite effect on vertebroarterial cervical spondylopathy.

Effect of Two Chinese Medicinal Compounds,Blood-Activating and Water-Draining Medicine,on Tumor Necrosis Factor α and Nuclear Factor κ B Expressions in Rats with Intracerebral Hemorrhage

Objective：To investigate the effect of blood-activating Chinese medicinal compounds and waterdraining Chinese medicinal compounds on tumor necrosis factor alpha（TNF-α）and nuclear factor kappaB（NF-κB）expressions in rats with intracerebral hemorrhage（ICH）at the acute stage,and to monitor their therapeutic effect and mechanism of action on inflammation and cerebral edema.Methods：A rat model of cerebral hemorrhage was achieved by injecting autologous arterial blood into the caudate nucleus.A total of 168 rats were randomly divided into 4 groups：blood-activating medicine group（n=42）,water-draining medicine group（n=42）,sham operated group（n=42）,and the model group（n=42）.A series of brain samples were obtained at days 1,3 and 5 after ICH from rats in all groups.Protein expression levels of TNF-αand NF-κB were measured by immunohistochemical staining and gene expression levels of TNF-αand NF-κB were measured by real-time fluorescent PCR.Results：Compared to the sham operated group,protein expression levels of TNF-αand NF-κB in the model group significantly increased（P〈0.01）.Protein and gene expressions of TNF-αfrom the blood-activating medicine group and water-draining medicine group significantly decreased when compared to those in the model group（P〈0.05）.Meanwhile,compared to the model group,the expression of NF-κB in the blood-activating medicine group significantly decreased（P〈0.05）,while expression of NF-κB in the water-draining medicine group did not differ（P〉0.05）.Conclusions：Blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds can alleviate inflammation of peripheral tissue and cerebral edema.However,the blood-activating Chinese medicinal compounds were more effective than the water-draining Chinese medicinal compounds.The possible effective mechanism may be by means of inhibiting the activation of NF-κB so as to suppress the transcription of target genes including gene expression of TNF-α.

Metabolic Regulatory and Anti-oxidative Effects of Modified Bushen Huoxue Decoction(补肾活血方) on Experimental Rabbit Model of Osteoarthritis

Objective： To observe the metabolic, regulatory and anti-oxidative effects of modified Bushen Huoxue Decoction （BSHXD, 补肾活血方）, a Chinese herbal medicine for Kidney （Shen）-reinforcement and bloodactivation, on an osteoarthritis （OA） rabbit model. Methods： A rabbit model for knee joint OA was established by the classic Huith＇s method. The OA model rabbits were randomized into 5 groups： the model control group, the positive control group treated with glucosamine sulfate, and the three BSHXD treated groups treated respectively with low, moderate, and high doses of BSHXD. In addition, a normal control group and a sham-operated group were set up. Experimental animals were sacrificed after a 7-week treatment, and pathological changes in cartilaginous tissue were estimated using the Mankin criteria. Hydroxyproline （Hyp） and malonaldehyde （MDA） contents in blood serum and urine, as well as superoxide dismutase （SOD） activity and nitric oxide （NO） content in blood serum and knee joint synovial homogenates were detected. Results： Mankin scoring showed insignificant statistical differences between the various treatment groups （P〉0.05）, but all were better than the model control group （P〈0.05）. Serum and udnary contents of Hyp and MDA as well as serum and synovial levels of NO were significantly lower, but the SOD activity in blood serum and synovial tissue was higher in the BSHXD treated groups than in the model group （P〈0.01）; the effect of BSHXD was dose-dependent to some extent. Coaclasloa： The modified BSHXD shows an effect of improving cartilage metabolism in experimental rabbits with OA, and possesses osteo-chondric protective effects in antagonizing peroxidation injury.

Treatment of Posthepatitic Cirrhosis by Fuzheng Huayu Tablet(扶正化瘀片) for Reinforcing Qi and Resolving Stasis

Objective： To investigate the efficacy and safety of the Fuzheng Huayu Tablet （扶正化瘀片, FZHYT）, which is used to reinforce qi and resolve stasis in patients with posthepatitic cirrhosis （PHC）. Methods： A multicenter, randomized, controlled clinical trial was conducted in 180 patients with PHC. The patients were randomly assigned using random numbers to a treatment group treated with FZHYT and a placebo group; the treatment course was 6 months for both groups. Overall response, adverse events （AEs）, and the 2-year survival rate were assessed after treatment. Evaluations were made on changes in liver function, liver fibrosis, coagulation, hemodynamics, degrees of esophagogastric varices, ascites, quality of life （QOL）, and scores of main symptoms. Results： The overall response was significantly higher in the treatment group than the placebo group （86.7% vs. 62.2%, P〈0.01）. Patients in both groups had significant improvements in liver function [total bilirubin （TBIL）, albumin （ALB）], liver fibrosis [hyaluronic acid （HA）, type 1V collagen （CIV）], coagulation [prothrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen （FIB）, and thrombin time （TT）], hemodynamics portal venous flow （PVF）, and splenic vein flow （SVF） after treatment. Between-group comparisons showed that compared with the placebo group patients in the treatment group achieved significantly greater improvements in TBIL, ALB, HA, C IV, PT, AP＇I-r, PVF, SVF, time to ascites resolution, 2-year survival, QOL, and symptom scores （P〈0.05 or P〈0.01）. There were no significant AEs during the treatment. Conclusion： FZHYT is effective and safe for the treatment of hepatic cirrhosis as it is associated with improved liver function, liver fibrosis, coagulation, portal hypertension state, QOL, 2-year survival rate, and fewer AEs.

Clinical effect of Jiutengzhuyu tablets on promoting blood circulation in women with oviducal obstruction

OBJECTIVE： To test the clinical curative effect of Jiutengzhuyu tablets, a patented Chinese vine-de- rived drug used for promoting blood circulation, on women with oviducal obstruction. METHODS Patients with tubal infertility were di- vided randomly into two groups： 58 patients in the treatment group and 57 in a control group. The treated patients took Jiutengzhuyu tablets orally for 25 days. The control group received an intrauter- ine infusion of 5 mg dexamethasone sodium phos- phate, 4000 units of chymotrypsin, 80 000 units of gentamicin sulfate dissolved in 20 mL of normal sa- line at I mL/min. After 3 months of treatment, the curative effect on tubal patency was assessed and a l-year follow-up visit was used to document any pregnancies. RESULTS The total effective rate was 78% in the treatment group and 32% in the control group with a statistically significant difference （x2=24.57, P〈0.01）.CONCLUSION： Jiutengzhuyu was effective in treat- ing infertility caused by tubal infertility with a Traditional Chinese Medicine diagnosis of blood stasis.

Chinese patent medicine for chronic obstructive pulmonary disease based on principles of tonifying Qi, promoting blood circulation by removing blood stasis, and resolving phlegm: a systematic review of randomized controlled trials

OBJECTIVE: To assess the efficacy and safety of Chinese patent medicine(CPM) with the principle of tonifying Qi, promoting blood circulation by removing blood stasis, and resolving phlegm(TQ-PBC-RP)in the management of stable chronic obstructive pulmonary disease(COPD).METHODS: A systematic review of randomized controlled trials(RCTs) identified from electronic databases and print was conducted. RCTs testing CPMs with TQ-PBC-RP against any type of controlled intervention in patients with stable COPD and assessing clinically relevant outcomes were included. Methodological quality was evaluated with the risk of bias tool according to systematic review handbook 5.0.2. Quality of evidence was estimatedby the rating approach developed by the Grading of Recommendations, Assessment, Development,and Evaluation Working Group.RESULTS: Thirteen eligible RCTs with 12 oral CPMs were tested. Significant differences between groups in favor of CPMs were not reported in all trials. Most trials included were deemed to be of low methodological quality with poor evidence quality.Because of large data heterogeneity, statistical pooling was not performed for all outcomes.CONCLUSION: The effectiveness of CPM in the treatment of stable COPD is not supported by evidence. Currently, evidence from RCTs is scarce and methodologically weak. Considering the popularity of CPMs among patients undergoing COPD, rigorously designed trials are warranted.

Protective Effects of Xiongshao Capsule(芎芍胶囊) on Anti-inflammatory Function of High-Density Lipoprotein in AnAtherosclerosis Rabbit Model

Objective： To observe the effects of Xiongshao Capsule（芎芍胶囊, XSC） on anti-inflammatory properties of high-density lipoprotein（HDL）, myeloperoxidase（MPO） and paraoxonase 1（PON1） in serum of atherosclerosis（AS） rabbit model and explore the anti-inflammatory protective effects of XSC on HDL. Methods： Sixty rabbits were randomized into the control, the model, XSC low-, medium-and high-dose（Rhizoma Chuanxiong ＋ Radix Paeoniae rubra ： 0.6＋0.3, 1.2＋0.6, 2.4＋1.2 g·kg-1·day-1, respectively）, and simvastatin（1 g·kg-1·day-1） groups. The model rabbits were fed with high-fat diet and respective drugs for 15 weeks. The blood and thoracic aortas samples were collected at the end of 15 weeks. The levels of serum MPO and PON1 as well as total cholesterol（TC） and free cholesterol（FC） in aorta wall cells were tested by enzyme linked immunosorbent assay. Results： TC and FC in the model group were significantly higher than those in the control group（P〈0.01）. Compared with the model group, TC and FC in the XSC groups were significantly lower（P〈0.05 or P〈0.01）, so was simvastatin group（P〈0.01）. There was no significant difference in PON1 level between groups（P〉0.05）, even between model and control groups（P〉0.05）. The serum MPO level in the model group was significantly higher than that in the control group（P〈0.05）, which was significantly lower in XSC groups as well as simvastatin group（P〈0.05 or P〈0.01）, and no difference was found between XSC groups and simvastatin group（P〉0.05）. Conclusions： XSC can reduce the serum MPO level in AS rabbits to protect the anti-inflammatory function of HDL, maintaining the normal lipid transport function. TC and FC levels in aorta cells decline, and this process initiated by XSC plays an anti-AS role.